Microglia protein profiles in CSF across Alzheimer's disease clinical stages.
Level 3 - non-randomized controlled study
Observational cross-sectional cohort study of human CSF biomarkers across disease stages
PubMed 41814022 · doi:10.1038/s43587-026-01088-0
What was done
Analyzed cerebrospinal fluid (CSF) samples from two cohorts totaling 834 participants spanning cognitively unimpaired controls, preclinical Alzheimer's disease (AD), and AD dementia. The authors measured microglia-related proteins, conducted functional enrichment analyses across disease stages, compared in vivo CSF protein changes to ex vivo microglial transcriptomic signatures (including disease-associated microglia phenotypes), and defined an 18-protein panel differentiating preclinical from dementia stages.
What was found
The authors identified 109 dysregulated microglia-related proteins in CSF across stages. Preclinical AD was enriched for innate immune processes and cellular recruitment, whereas AD dementia was enriched for adaptive immunity and macrophage responses. Microglia transcriptomic signatures spanned both stages rather than being stage-specific. An 18-protein panel was classified to highlight distinct transitions between stages. The abstract reports no numerical effect sizes, fold-changes, p-values, or diagnostic performance metrics.
Why it matters
This study provides evidence that microglial involvement evolves from early innate immune activity to later adaptive immune pathways across clinical stages of AD. These stage-dependent CSF protein profiles provide candidate fluid biomarkers for staging disease progression and tracking microglia-targeted interventions.
Limits
The abstract reports no numerical statistics, effect sizes, diagnostic accuracy metrics (such as AUC or sensitivity/specificity), or cohort demographic details. The cross-sectional design across stages precludes tracking within-person temporal trajectories, and findings require independent longitudinal validation.
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